Improved formulations of antisense oligodeoxynucleotides using wrapped liposomes.

Previously, we demonstrated that wrapping dextran fluorescein anionic/cationic lipid complexes with neutral lipids produced a stable formulation that markedly increased the duration of the compound in plasma after intravenous administration to rats. The improved drug-delivery properties of the wrapped liposomes (WL) relative to other formulations suggested that this technology could offer important advantages for the administration of other polyanionic drugs, including antisense oligodeoxynucleotides (ODN). In the present study, we investigated the value of WL for formulating fluorescence-labeled phosphorothioated ODN (F-ODN). WL encapsulating F-ODN/cationic lipid complexes were prepared efficiently using similar methodology to that used in our earlier study. Studies confirmed that these WL were stable in vitro. Following intravenous administration to mice, free F-ODN and naked F-ODN/cationic lipid complexes were rapidly eliminated whereas administration of the WL resulted in high blood concentrations of drug that were maintained for several hours. Additional studies were conducted in mice that were inoculated with tumor cells (Caki-1 xenograft model, human kidney); in these experiments, intravenous administration of WL delivered 13 times more F-ODN to the tumor site than achieved after injection of free F-ODN.     

Solitary fibrous tumor of the inguinal region

Solitary fibrous tumors (SFT) have recently been established to be of mesenchymal origin. Although there are numerous reports of SFTs arising from the pleura, reports of the tumor arising from extrapleural sites are comparatively rare [Fletcher CDM, Unni K, Mertens F (eds) World Health Organization classification of tumors, pathology & genetics, tumors of soft tissue and bone. IARC Press, Lyon, pp 86–901, 2002]. We report a case of SFT arising in the inguinal region.     

Anal metastasis from carcinoma of the lung: Report of a case

We report herein the case of a 75-year-old man who developed anal canal metastasis from squamous cell carcinoma of the lung. Initially, he underwent a right middle and lower lobectomy combined with left atrial wall resection under cardiopulmonary bypass. He presented 3 months later with an anal polyp which had prolapsed and bled, for which he underwent a transanal polypectomy. Histologically, the polyp was classified as squamous cell carcinoma and considered to be a metastasis from the primary lung cancer. He is presently well with no signs of recurrence 9 months after his initial operation. To our knowledge, there has been no other case of anal metastasis from lung cancer ever reported.     

The biphasic response of hepatic arterial blood flow caused by vasoactive substances--an experimental study in dogs]

In ten male mongrel dogs, blood flow was measured in the common hepatic artery (CHA), portal vein (PV) and liver tissue before and after the injection of vasoactive substances: angiotensin II (1.0 micrograms/kg), prostaglandin F2 alpha (1.0 micrograms/kg) and vasopressin (0.1 Unit/kg), under observation of the systemic circulation. Each injection caused a biphasic response in CHA blood flow, an initial decrease followed by a marked increase, while PV blood flow decreased. Liver tissue blood flow was reduced just after injection, but soon returned to a normal level. The duration of action was the shortest with prostaglandin F2 alpha and the longest with vasopressin. In using vasoactive substances in pharmaco-angiography, it is important to consider the biphasic response in CHA blood flow as well as the duration of action of these substances.     

AC/A ratios in myopic and emmetropic Hong Kong children and the effect of timolol§

Purpose: Caucasian children with myopia have elevated response accommodative vergence to accommodation (AC/A) ratios. The purpose of this study was twofold: to determine if response AC/A ratios vary with refractive error and with myopic progression rate in Hong Kong Chinese children, and to determine the effect of beta‐adrenergic antagonism with topical timolol application on AC/A ratios. Methods: Thirty children aged eight to 12 years participated in the study. All refractive errors were corrected with spectacle lenses. Accommodative responses were measured using a Shin‐Nippon autorefractor and concurrent changes in vergence were assessed using a vertical prism and a Howell‐Dwyer card at three metres and 0.33 metre. Accommodative demand was altered using plus or minus two dioptre lenses and lens‐ and distance‐induced response AC/A ratios were calculated. Measurements were repeated 30 minutes after the instillation of topical timolol maleate (0.5 per cent). Results: AC/A ratios appeared higher in progressing myopic children but the difference was not statistically significant. Timolol application reduced accommodative convergence (AC) in the stable myopes (reduction = ‐3 ± 1.14^A) but not in the emmetropes (0.69 ± 0.9^P) or progressing myopes (0.16 ± 0.43^A) and this difference between refractive groups was statistically s ignificant (F^2,27= 3.766; P= 0.036). However, timolol did not produce a significant change in the accommodative response to positive or negative lenses or response AC/A ratios. Conclusions: We did not find that AC/A ratios in myopic Chinese children were elevated and therefore, it is unlikely that elevated AC/A ratios are responsible for the high levels of myopia that occur in Hong Kong. The finding that timolol reduced AC in the stable myopes suggests that the autonomic control of accommodative convergence in these children may be different from that in emmetropic children and those with progressing myopia.     

Activation of guinea pig eosinophil respiratory burst by leukotriene B4: role of protein kinase C

Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C.